Electrical stimulation of cranial nerves and/or spinal nerves is a strategy for diagnosing and treating various medical conditions based on the principle that neuromodulation of these nerves induces significant and consistent changes in the brain through brainstem projections. Many of these stimulation techniques act by modulating the activity of cervical spinal and cranial nerve sensory afferents and other fibers projecting back to brainstem regions (e.g., to regulate the activity of the reticular activating system and other bottom-up pathways known to affect cortical gain and psychophysiological arousal). Vagal nerve stimulation at various sites in the head, neck, and upper body is known to have widespread clinical application including for neurological, cardiovascular, pulmonary, renal, hepatic, and immunological disorders.
Implanted cranial or spinal nerve electrical stimulators are generally well localized to targeted nerves, including those in areas of the head generally covered by hair, and can use lower stimulation intensities due to the proximity of the targeted nerve and absence of insulating skin. Though effective, surgical implantation of electrodes is costly and is associated with normal surgical risks. In at least some instances, implanted cranial and/or cervical spinal nerve stimulators cause side effects including difficulty swallowing and hoarseness of the voice.
Transdermal cranial and/or cervical spinal nerve electrical stimulators require less intervention, lower cost, and offer a better safety profile relative to implanted systems. However, transdermal stimulation strategies are believed to be less than optimal in some circumstances, for instance: the targeting of cranial and/or cervical spinal nerves that vary between patients; the difficulty of delivering current comfortably and efficiently through the skin; and skin discomfort mediated by sensory receptors that limits the intensity (or other parameters) of stimulation.
For example, the Electrocore gammaCore® stimulator is a handheld device that targets the vagal nerve in the neck. U.S. Pat. No. 8,843,210 to inventors Simon et al. describe a neck-based stimulation system. This form factor is lacking in terms of miniaturization and ease of use, particularly hands-free use, limiting the activity of users during stimulation and the available contexts for stimulation (i.e. it is difficult to apply handheld stimulation while driving, holding a child, riding a bike, or even eating a meal).
Targeting transdermal electric stimulation (TES) to the pinna may overcome some of these limitations. The pinna generally has little or no hair and several cranial and cervical spinal nerves project to this portion of the ear. Electrical stimulation of branches of the vagal, trigeminal, and facial nerves in the pinna has been described previously. Fewer descriptions exist for targeting cervical spinal nerves (for example the greater auricular nerve) projecting to this region to modulate brain activity. Existing Pinna Electrical Nerve Stimulation (PENS, also referred to as auricular electrical stimulation, auricular TES, auricular stimulation, or auricular electrical nerve stimulation) and methods are not optimal at least because they have not proven effective and reliable for regular use, particularly by untrained users. The waveforms, electrode composition, and mechanical-geometric structures for dermal application of electrodes on the pinna have not yet been able to effectively deliver comfortable waveforms that induce beneficial and significant cognitive effects, and, in some cases, non-cognitive effects. Additionally, systems and methods optimized for stimulating combinations of cranial nerves (trigeminal, facial, and/or vagal) and cervical spinal nerves (greater auricular nerve; C2-3) projecting to this region to modulate brain function do not presently exist. For example, electrode compositions for pinna nerve stimulation that distribute charge uniformly on the targeted skin area and buffer pH changes in the skin would be beneficial improvements on available systems.
Various therapeutic and diagnostic applications of auricular electrical stimulation have been described. In some instances, consumer applications (i.e. ‘lifestyle’ applications not intended to diagnose or treat any medical condition) for auricular electrical stimulation would be beneficial. For these applications in particular, though also for many therapeutic and diagnostic applications, it may be beneficial for stimulation to be more comfortable—and to induce noticeable and beneficial effects in healthy users. Existing systems and methods are lacking in this regard.
For example, U.S. Pat. No. 5,144,952 to inventors Frachet and David describes an earring pierced through the pinna for transcutaneous electrical stimulation. Though this form factor is minimally invasive (at least with respect to individuals with cosmetic ear piercings), less invasive apparatuses for electrical stimulation of the pinna would be more comfortable and avoid the potential for infection. In at least some instances, this method may be limited because it delivers highly localized stimulation of particular afferents, whereas broader stimulation of zones innervated by cranial and cervical spinal nerves could induce more robust cognitive effects.
Electrostimulation via ear clips is one standard noninvasive means for TES of the pinna. However, the ear clips are generally positioned on the ear lobe, a region with more fatty tissue that causes ear clips to generally have high impedance and limit the intensity of stimulation, as well as the efficacy of neuromodulation of the branches of cranial nerves in the pinna more distant from the ear lobe. Again, the highly localized site of stimulation may preclude some outcomes where more diffuse and global stimulation of several regions of the pinna simultaneously could overcome this limitation. For example, systems and methods for simultaneously stimulating the helix, triangular fossa, and cymba conchae may be beneficial for inducing more prominent changes in psychophysiological arousal than simply stimulating the tragus or ear lobe.
U.S. Pat. No. 5,514,175 to inventors Kim et al. describes a lightweight, portable auricular TES system using bipolar waveforms including those with frequencies of 15 Hz, 500 Hz, and 15,000 Hz and, for example, peak intensity of 150 μA. A key feature of the system described by Kim et al. is low voltage operation (i.e. 2 volts or less, 10 volts or less). The inventors in the present case have found that such low peak stimulation intensities are limiting for robust neuromodulation of cranial and/or cervical spinal nerves and are not able to induce significant and beneficial physiological and/or cognitive effects. Moreover, the low voltage operation of the systems described by Kim et al. are unsuitable for higher current intensities (e.g. above about 1 mA) due to high skin impedance for small electrodes in the relatively well insulated pinna.
In yet another example, Cerbomed GmBH sells the Nemos® transcutaneous vagal nerve stimulator with an earphone-style assembly containing a pair of electrodes targeting vagal nerve endings in the conch of the ear. Patients carry out stimulation autonomously about 4 hours per day for the treatment of epilepsy. The intensity of stimulation is set by the user and delivered at (for example) 250 μsec pulses at 25 Hz at an intensity that causes slight tingling, generally 2 mA or less.
Patents originally assigned to Cerbomed describe auricular stimulation systems and methods for using them that are lacking in at least some instances for delivering comfortable transdermal electrical stimulation that induces a significant and beneficial cognitive effect. In at least some instances, the auricular stimulation systems disclosed by Cerbomed are lacking because they do not incorporate the use of transducers or speakers (headphones for example) for introducing naturalistic stimulation, such as music or sounds.
U.S. Pat. No. 8,506,469 to Deitrich et al describes “a monophasic-modified rectangle impulse with a pulse width of 250 ms, electrical current amplitude between 4 mA and 8 mA stimulation frequency of 25 Hz is used.” Also described are pinna stimulation waveforms that are either monopolar or bipolar and in a preferable frequency range of 0.01 to 1000 Hz. However, these auricular transdermal electrical stimulation waveforms are suboptimal in at least some instances for comfortable stimulation at high peak intensities (and with other appropriate waveform parameters) that induce a significant and beneficial cognitive effect.
U.S. Pat. No. 8,688,239 to Hartlep et al. shows an auricular electrical stimulation apparatus with mechanical and geometric features for stable placement in a patient's ear (in the conch) for targeting the auricular branch of the vagal nerve. However, these apparatuses are not configured to use disposable electrodes, including disposable electrodes that include consumptive electrochemistry to improve skin comfort at higher peak stimulation intensities that induce stronger cognitive effects, in at least some instances.
Erfan disclosed a bilateral headset auricular stimulator in U.S. application US2005/0165460 wherein the hardware device hangs as a necklace from a patient's ears similar to a marketed product from Auri-Stim Medical, Inc.
U.S. Pat. No. 8,639,343 to de Vos describes an apnoea treatment that couples measurement of breathing to auricular electrical stimulation at less than 500 Hz.
The products and patent art of Cerbomed, de Vos, and Auri-Stim Medical, Inc. are lacking in the effects induced by stimulation of the pinna, as well as the intensity of stimulation achievable without skin discomfort. New systems for stimulation of cranial and/or cervical spinal nerve projections in the pinna (also referred to as the auricle) that are comfortable at higher peak stimulation intensities and induce beneficial cognitive effects would be desirable.
It would generally be advantageous to provide devices and methods that allow transdermal electrical stimulation of the pinna in a manner that overcomes the problems with pain and efficacy. In particular, it would be beneficial to provide auricular TES devices and methods for modulating (e.g., inducing, enhancing, reversing, or otherwise increasing or changing) a cognitive effect and/or mental state. For example, TES stimulation protocols and electrode configurations that induce a relaxing, calming, anxiolytic, dissociated, high mental clarity, or worry-free state of mind in a subject would be advantageous for improving the subject's experiences and state of mind, as well as addressing insomnia and mitigating negative responses to stress. Similarly TES stimulation protocols and apparatuses that increase a subject's motivation, alertness, subjective (and/or physiological) energy level, or focus would be advantageous for improving a subject's productivity, frequency of physical activity, and providing beneficial states of mind. Due to the way the brain integrates multimodal sensory information, it would be beneficial to provide devices and methods that enable the stimulation of cranial and cervical spinal nerves projecting to the pinna simultaneously combined with naturalistic auditory stimulation, such as music to affect motivation, mood, psychophysiological arousal, and cognition. Described herein are methods and apparatuses (including devices and systems) and methods that may address the problems and opportunities discussed above. Also described herein are methods for treating or diagnosing a subject with auricular TES systems. Electrical stimulation waveforms that activate nerves in the ear (pinna) while causing minimal or limited discomfort would be beneficial for pinna electrical stimulation and are described herein. Conductive form factors that fit comfortably in the ear and provide a generally uniform and/or pH buffering electrode composition would provide an additional benefit and are also described herein.
The various disclosed auricular stimulation systems are further lacking with regard to miniaturization and portability. For lifestyle applications, as well as clinical (i.e. therapeutic or diagnostic) applications, hands-free application with a lightweight, minimally-distracting or intrusive form factor would enhance the ease-of-use and applications for the auricular stimulation system. Systems that are small, lightweight and wearable in an ear (i.e. within the concha and/or triangular fossa), on an ear, or adhesively attached on or near the ear would provide additional benefit relative to handheld systems and systems that require a dedicated handheld or table-top control unit. One system design that enables a smaller neurostimulator control unit is to offload some of the control software and/or power source requirements to a portable user computing device (i.e. a smartphone, smartwatch, or tablet) by coupling to a connector of the portable user computing device with a cable.